PPEF2 (protein phosphatase with EF-hand domain 2) is a calcium-dependent serine/threonine phosphatase that regulates multiple cellular processes through its dual calcium-sensing mechanisms. The protein functions through both C-terminal EF-hand calcium-binding domains and N-terminal calmodulin-binding IQ motifs, enabling Ca2+-dependent interaction with calmodulin with nanomolar affinity 1. PPEF2 plays a critical role in mitochondrial quality control by dephosphorylating phospho-S65 ubiquitin, thereby opposing PINK1-mediated mitophagy and suppressing mitochondrial degradation pathways 2. In retinal function, PPEF2 is essential for photoreceptor survival and visual function, with its translation enhanced by YTHDC2-mediated m6A RNA modification 3. The protein is strongly expressed in retinal tissues, particularly in photoreceptor inner segments and outer nuclear layer 4. Clinically, PPEF2 variants are associated with high myopia, where mutations reduce protein levels and affect cell migration, proliferation, and apoptosis 4. Additionally, PPEF2 variants have been implicated in schizophrenia risk through effects on NMDA receptor signaling pathways 5, and the gene shows preferential expression in dendritic cells 6. PPEF2 also contributes to neuroprotection in Parkinson's disease through MAPK pathway regulation 7.